Registration Dossier

Administrative data

Description of key information

Skin irritation / Corrosion.

Two studies were evaluated on this endpoint as follows:

> A Skin Corrosion Test on rabbits according to the regulations of the Department of Transportation

No erythema or edema was observed at 4, 24, or 48 hours.

> A Primary Irritation Test on Guinea Pigs

A 10% solution of the test substance in DMAC caused mild and strong irritation, respectively, on the intact skin of guinea pigs. However control tests with the solvent produced strong erythema on both groups of guinea pigs.  It was therefore concluded that the effects observed were due to DMAC and that the test compound caused little or no irritation. 

Eye irritation.

Two studies were available on this endpoint as follows:

> In vitro test:

A study was performed to assess the ocular irritancy potential of the test material to the isolated bovine cornea. The neat test material was applied for 240 minutes. Negative and positive control materials were tested concurrently.The test material was considered not to be an ocular corrosive or severe irritant.

> In vivo test:

After treating with the test substance, washed and unwashed rabbit eyes had slight corneal clouding. The unwashed eye also displayed mild conjunctivitis. Both eyes were normal 1 day after treatment. This material may therefore cause mild ocular effects, however these are not deemed severe enough to result in classification or labelling.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
November , 1973
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Remarks:
Non-GLP. Conducted to a recognised methodology; however lack of full assessment data and age of report results in deficient study. Therefore it is considered that this data can be utilised in conjunction with other skin data as a weight of evidence approach, on animal welfare grounds. This study is proposed as the key study, as the results are conducted on the substance alone to a recognised test method.
Qualifier:
according to
Guideline:
other: Department of Transportation, Hazardous Materials Regulations Board, Docket No. HM-57, Federal Register, Vol. 33, No. 28, Section 173.240, February 12, 1973.
Deviations:
no
Principles of method if other than guideline:
Skin corrosion assessment in 6 test subjects (rabbit)
GLP compliance:
no
Specific details on test material used for the study:
4,4'-oxydianiline
4,4'-diaminodiphenyl ether
CAS 101-80-4
Species:
rabbit
Strain:
not specified
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Not specified.
- Age at study initiation: Not specified.
- Weight at study initiation: 2 to 3 kg
- Housing: Not specified.
- Diet (e.g. ad libitum): Not specified.
- Water (e.g. ad libitum): Not specified.
- Acclimation period Not specified.


ENVIRONMENTAL CONDITIONS
- Temperature (°C): Not specified.
- Humidity (%): Not specified.
- Air changes (per hr): Not specified.
- Photoperiod (hrs dark / hrs light):Not specified.


IN-LIFE DATES: Not specified.
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5g
- Concentration (if solution): Not applicable


VEHICLE: None
Duration of treatment / exposure:
4 hours
Observation period:
48 hours
Number of animals:
6
Details on study design:
TEST SITE
- Area of exposure: Not specified
- % coverage: Not specified
- Type of wrap if used: 1.5 by 1.5 inch, 12-ply cotton gauze pads and the trunk of each rabbit was then loosely wrapped with rubber sheeting


REMOVAL OF TEST SUBSTANCE
- Washing (if done): Yes, unspecified but assumed to be water.
- Time after start of exposure: 4 hours


SCORING SYSTEM: Visual
Irritation parameter:
erythema score
Basis:
animal: 1 to 6
Time point:
other: mean score for 24 and 48h.
Score:
0
Reversibility:
other: not applicable
Remarks on result:
other: Mean score from the six animals at 24 and 48h. No results available at 72h. No individual data available.
Irritation parameter:
edema score
Basis:
animal: 1 to 6
Time point:
other: mean score for 24 and 48h.
Score:
0
Reversibility:
other: not applicable
Remarks on result:
other: Mean score from the six animals at 24 and48h. No results available at 72h. No individual data available.
Irritation parameter:
erythema score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Reversibility:
other: Not applicable
Remarks on result:
other: No effects observed
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Reversibility:
other: Not applicable
Remarks on result:
other: No effect observed
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
24 h
Score:
0
Reversibility:
other: Not applicable
Remarks on result:
other: No effects observed
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
48 h
Score:
0
Reversibility:
other: Not applicable
Remarks on result:
other: No effects observed
Irritation parameter:
edema score
Time point:
72 h
Remarks on result:
not measured/tested
Irritation parameter:
erythema score
Time point:
72 h
Remarks on result:
not measured/tested
Irritant / corrosive response data:
The test animals displayed no effects as a result of the treatment
Other effects:
None

No erythema or edema was observed at 4, 24, or 48 hours. Skin corrosion was not observed in any of the animals tested.

Interpretation of results:
GHS criteria not met
Conclusions:
No effects were displayed in any of the 6 test animals used, hence it is concluded that the test material is not corrosive to rabbit skin.
Executive summary:

No erythema or edema was observed at 4, 24, or 48 hours. Skin corrosion was not observed in any of the animals. According to the regulations of the Department of Transportation, 4,4’-oxydianiline was not considered a corrosive material.

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Remarks:
Non-GLP. A scientifically defensible approach was utilised for this test; however no fixed methodology was cited within the report. This is presumed due to the age of the report. However, the results of this test are considered appropriate for use, as a weight of evidence approach.
Qualifier:
no guideline followed
Principles of method if other than guideline:
The substance, as a 10% w/w solution in dimethylacetamide (DMAC), was applied to the shaved intact skin of 9 or 10 albino guinea pigs. Observations were made after 24 hours contact. A control test with DMAC was performed on each animal in the same way.
GLP compliance:
no
Specific details on test material used for the study:
4,4'-oxydianiline
4,4'-diaminodiphenyl ether
CAS 101-80-4
Species:
guinea pig
Strain:
not specified
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Not specified.
- Age at study initiation: Not specified.
- Weight at study initiation: Not specified.
- Housing:Not specified.
- Diet (e.g. ad libitum): Not specified.
- Water (e.g. ad libitum): Not specified.
- Acclimation period: Not specified.


ENVIRONMENTAL CONDITIONS
- Temperature (°C): Not specified.
- Humidity (%): Not specified.
- Air changes (per hr): Not specified.
- Photoperiod (hrs dark / hrs light): Not specified.


IN-LIFE DATES: Not specified.
Type of coverage:
not specified
Preparation of test site:
shaved
Vehicle:
other: Dimethylacetamide (DMAC)
Controls:
yes, concurrent vehicle
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): N/A
- Concentration (if solution): 10% w/w (presumed - unspecified definitively)


VEHICLE
- Amount(s) applied (volume or weight with unit): Not specified.
- Concentration (if solution): Not specified.
- Lot/batch no. (if required): Not specified.
- Purity: Not specified.
Duration of treatment / exposure:
24 hours
Observation period:
At 24 hours
Number of animals:
10 - Substance and vehicle.
9 - Vehicle only.
Details on study design:
The substance, as a 10% w/w solution in dimethylacetamide (DMAC), was applied to the shaved intact skin of 10 albino guinea pigs. Observations were made after 24 hours contact. A control test with DMAC was performed on each animal in the same way.

TEST SITE
- Area of exposure: Not specified
- % coverage: Not specified
- Type of wrap if used: Not specified


REMOVAL OF TEST SUBSTANCE
- Washing (if done): Not specified
- Time after start of exposure: 24 hours


SCORING SYSTEM: Visual assessment
Irritation parameter:
erythema score
Basis:
other: Animals treated with the test substance (10% w/w solution in DMAC)
Time point:
24 h
Reversibility:
no data
Remarks on result:
other: 3 incidences of strong erythema; 1 incidence of mild erythema; 6 negative responses
Irritation parameter:
erythema score
Basis:
other: Negative controls (Animals treated with only DMAC)
Time point:
24 h
Reversibility:
not specified
Remarks on result:
other: 3 incidences of strong erythema; 3 incidence of moderate erythema; 2 incidence of mild erythema; 1 negative response
Irritant / corrosive response data:
After 24 hours exposure to the substance in a 10% w/w solution in DMAC, 3 incidences of strong erythema and 1 of mild were noted in the test animanimals. Six negative responses were noted.

For the test solvent, DMAC, after 24 hours three strong, three moderate and two mild incidents of erythema were noted. One negative response was also noted.

Effects after 24 hours exposure:

Solution

Results as specified.

10% solution of 4,4’-Oxydianiline in DMAC

three strong and one mild erythema, six negative

 

DMAC only

three strong, three moderate and two mild erythema, one negative

 

Interpretation of results:
GHS criteria not met
Conclusions:
The 10% solution of 4,4'-oxydianiline in DMAC caused mild and strong irritation, respectively, on the intact skin of guinea pigs. Control tests with the solvent produced strong erythema on both groups of guinea pigs.
It was therefore proposed that the test compound caused little or no irritation per se, and appeared to lessen the irritative effect of DMAC.
Executive summary:

The substance, as a 10% w/w solution in dimethylacetamide (DMAC), was applied to the shaved intact skin of 10 albino guinea pigs. Observations were made after 24 hours contact. A control test with DMAC was performed on each animal in the same way.

The 10% solution of 4,4'-oxydianiline in DMAC caused mild and strong irritation, respectively, on the intact skin of guinea pigs. Control tests with the solvent produced strong erythema on both groups of guinea pigs.

The irritancy effects noted within this study are proposed to be related to the solvent only, and not to the substance itself. Therefore the test compound is considered to cause little irritaion or not to cause irritation.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Referenceopen allclose all

Endpoint:
eye irritation: in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
11 February 2010
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 437 (Bovine Corneal Opacity and Permeability Test Method for Identifying Ocular Corrosives and Severe Irritants)
Principles of method if other than guideline:
A study was performed to assess the ocular irritancy potential of the test material to the isolated bovine cornea. The neat test material was applied for 240 minutes. Negative and positive control materials were tested concurrently. The two endpoints, decreased light transmission through the cornea (opacity) and increased passage of sodium fluorescein dye through the cornea (permeability) were combined in an empirically derived formula to generate an In Vitro Irritancy Score (MS).
GLP compliance:
yes
Specific details on test material used for the study:
4,4'-oxydianiline
4,4'-diaminodiphenyl ether
CAS 101-80-4
Species:
cattle
Strain:
not specified
Details on test animals or tissues and environmental conditions:
Eyes from adult cattle were obtained from a local abattoir as a by-product from freshly slaughtered animals. The eyes were excised by an abattoir employee and placed in Hanks' Balanced Salt Solution (HBSS), supplemented with Penicillin/Streptomycin, and transported to the laboratory on ice packs. The corneas were prepared immediately on arrival.
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
350 mg of the neat material was applied directly to cornea.
Duration of treatment / exposure:
240 minutes
Observation period (in vivo):
None - observed at end of treatment process.
Number of animals or in vitro replicates:
None - in vitro test. 3 bovine eyes were used for the test.
Details on study design:
4.1 – Pre-Test Procedures

4.1.1 Source of Bovine Eyes

Eyes from adult cattle were obtained from a local abattoir as a by-product from freshly slaughtered animals. The eyes were excised by an abattoir employee and placed in Hanks' Balanced Salt Solution (HBSS), supplemented with Penicillin/Streptomycin, and transported to the laboratory on ice packs. The corneas were prepared immediately on arrival.

4.1.2 Preparation of Corneas

All eyes were macroscopically examined before and after dissection. Only corneas free of damage were used.

The cornea from each selected eye was removed leaving a 2 to 3 mm rim of sclera to facilitate handling. The iris and lens were peeled away from the cornea. The isolated corneas were immersed (epithelial side uppermost) in a dish containing HBSS until they were mounted in Bovine Corneal Opacity and Permeability (BCOP) holders.

The anterior and posterior chambers of each BCOP holder were filled with complete minimum essential medium (MEM) and plugged. The holders were incubated at 32 +/- 1°C for at least 60 minutes. At the end of the incubation period each cornea was examined for defects. Only corneas free of damage were used.

4.1.3 Selection of Corneas and Opacity Reading

The medium from both chambers of each holder was replaced with fresh complete MEM.

A pre-treatment opacity reading was taken for each cornea using a calibrated opacitometer. The average opacity for all corneas was calculated.

Three corneas were numerically allocated to the test material. Three corneas were also numerically allocated to the negative control material and three corneas to the positive control material.

4.2 Treatment of Corneas

The MEM was removed from the anterior chamber of the BCOP holder. The window-locking ring and glass window from the anterior chamber were removed and the neat test material was evenly sprinkled over the cornea. 350 mg of the neat test material was found to adequately cover the cornea surface. After dosing, the glass window and locking ring were replaced and each holder was incubated, anterior chamber uppermost, at 32 +/- 1°C for 240 minutes.

At the end of the exposure period the window-locking ring and glass window were removed to allow the test material preparation or control material to be removed from the anterior chamber. The corneas were rinsed three times with fresh complete MEM containing phenol red before a final rinse with complete MEM. The anterior and posterior chambers were refilled with fresh complete MEM. A post-treatment opacity reading was taken and each cornea was visually observed.

4.3 Application of Sodium Fluorescein and Permeability Determinations

4.3.1 Application of Sodium Fluorescein

Following the opacity measurement the permeability of the corneas to sodium fluorescein was evaluated. The medium from the anterior chamber was removed and replaced with sodium fluorescein solution (5 mg/mL). The dosing holes were plugged and the holders incubated, anterior chamber uppermost, at 32 +/- 1°C for 90 minutes +/- 5 minutes.

4.3.2 Permeability Determinations

After incubation the medium in the posterior chamber of each holder was decanted and retained.

360 µl of medium representing each cornea was applied to a designated well on a 96-well plate and the optical density at 492nm (OD492) was measured.

If values greater than 1.500 OD492 were obtained a 1 in 5 dilution of the medium in complete MEM was performed and the measurement repeated. The modified value was multiplied by 5 to reflect the 1 in 5 dilution.

4.4 Histopathology

The corneas were retained after testing for possible conduct of histopathology. Each cornea was placed into a pre-labelled tissue cassette fitted with a histology sponge to protect the endothelial surface. The cassette was immersed in 10% neutral buffered formalin.
Irritation parameter:
in vitro irritation score
Value:
1.6
Negative controls validity:
valid
Positive controls validity:
valid
Other effects / acceptance of results:
EVALUATION OF RESULTS

Results from the two test method endpoints, opacity and permeability, were combined in an empirically derived formula to generate an In Vitro Irritancy Score.

- Opacity Measurement:
The change in opacity for each cornea (including the negative control) was calculated by subtracting the initial opacity reading from the final opacity reading. These values were then corrected by subtracting from each the average change in opacity observed for the negative control corneas. The mean opacity value of each treatment group was then calculated by averaging the corrected opacity values of each cornea for that treatment group.

- Permeability Measurement:
The corrected OD492 was calculated by subtracting the mean OD492 of the negative control corneas from the OD492 value of each treated cornea. The OD492 value of each treatment group was calculated by averaging the corrected OD492 values of the treated corneas for the treatment group.

In Vitro Irritancy Score:
The following formula was used to determine the in vitro score:

In Vitro Irritancy Score = mean opacity value + (15 x mean OD492 value)

Additionally, the opacity and permeability values were evaluated independently to determine whether the test material induced a response through only one of the two endpoints.

Visual Observation

The condition of the cornea was visually assessed immediately after rinsing and at the final opacity measurement.

DATA INTERPRETATION

A test material that induces an in vitro irritancy score >55.1 is defined as an ocular corrosive or severe irritant.

In Vitro Irritancy Score

The results are summarised as follows:

Treatment In Vitro Irritancy Score

Test Material 1.6
Negative Control 1.8
Positive Control 95.4

CONCLUSION

The test material was considered not to be an ocular corrosive or severe irritant.

Individual and Mean Corneal Opacity and Permeability Results

Treatment

Cornea Number

Opacity

Permeability (OD)

In vitro Irritancy Score

 

 

 

 

Pre-Treatment

Post-Treatment

Post-Treatment -Pre-Treatment

Corrected Value

-

Corrected Value

 

 

Negative Control

1

2

4

2

-

0.025

-

-

 

 

2

1

2

1

-

0.042

-

-

 

 

3

2

3

1

-

0.025

-

-

Mean

 

-

-

1.3*

-

0.031

-

1.8

Positive Control

7

2

75

73

71.7

2.285

2.254

-

 

 

8

1

62

61

59.7

1.925

1.894

-

 

 

9

1

62

61

59.7

2.220

2.189

-

Mean

-

-

-

-

63.7.

-

2.113*

95.4

Test Material

4

1

 

2

0.7

0.027

0.0

-

 

 

5

2

5

3

1.7

0.059

0.026

-

 

 

6

2

5

3

1.7

0.067

0.036

-

Mean

-

-

-

-

1.4.

 

0.021*

1.6

OD = Optical density

* = Mean of the post treatment - pre-treatment values                • = Mean corrected value Corneal Epithilium Opacity

Treatment

Cornea Number

Observation

 

 

 

 

Immediately after Rinsing

Negative Control

1

clear

2

clear

3

clear

Positive Control

7

cloudy

8

cloudy

9

cloudy

Test Material

4

clear

5

clear

6

clear

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test material was considered not to be an ocular corrosive or severe irritant.
Executive summary:

A study was performed to assess the ocular corrosivity potential of the test material to the isolated bovine cornea. This study was conducted according to the OECD guideline 437 "Bovine Corneal opacity and Permeability" (BCOP).

The test material was considered not to be an ocular corrosive or severe irritant.

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
10/20/81 - 10/23/81
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
Non-GLP. The study assesses only two rabbits resulting in the methodology being deficient. However, results and observations are fully documented and considered suitable for hazard assessment.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
only 2 organisms assessed.
Principles of method if other than guideline:
A dose of solid test material was placed into the right conjunctival sac of each of 2 male albino rabbits. After 20 seconds, 1 treated eye was washed with tap water for 1 minute. The treated eye of the other rabbit was not washed.
GLP compliance:
no
Specific details on test material used for the study:
4,4'-oxydianiline
4,4'-diaminodiphenyl ether
CAS 101-80-4
Species:
rabbit
Strain:
not specified
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Not specified
- Age at study initiation: Not specified
- Weight at study initiation: Not specified
- Housing: Not specified
- Diet (e.g. ad libitum): Not specified
- Water (e.g. ad libitum): Not specified
- Acclimation period: Not specified


ENVIRONMENTAL CONDITIONS
- Temperature (°C): Not specified
- Humidity (%): Not specified
- Air changes (per hr): Not specified
- Photoperiod (hrs dark / hrs light): Not specified


IN-LIFE DATES: From: 20 October 1981 To: 23 October 1981
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
10 mg as received
Duration of treatment / exposure:
A dose of 10 mg of solid test material was placed into the right conjunctival sac of each of 2 male albino rabbits. After 20 seconds, 1 treated eye was washed with tap water for 1 minute. The treated eye of the other rabbit was not washed.
Observation period (in vivo):
Observations of the cornea, iris and conjunctiva were made with an ophthalmoscope at 1 and 4 hours, and at 1, 2, and 3 days
Number of animals or in vitro replicates:
2 - one washed eye, one unwashed.
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): Yes, single animal only
- Time after start of exposure: 20 seconds


SCORING SYSTEM: Visual Observations of the cornea, iris, and conjunctiva were made with an ophthalmoscope at 1 and 4 hours, and at 1, 2, and 3 days


TOOL USED TO ASSESS SCORE: Eyes were stained with Fluor-i-strip and a slit-lamp biomicroscope was used at examinations after the day of treatment.
Irritation parameter:
cornea opacity score
Basis:
animal #1
Remarks:
Unwashed Eye
Time point:
other: 4 hours
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 24 hours
Remarks on result:
other: Small area of slight clouding at 1 hr. Decreasing to a local area at 4 hours.
Irritation parameter:
iris score
Basis:
animal #1
Remarks:
Unwashed eye
Time point:
other: 4 hours
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 1 hour
Remarks on result:
other: No effects noted
Irritation parameter:
conjunctivae score
Basis:
animal #1
Remarks:
Unwashed eye
Time point:
other: 4 hours
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 24 hours
Remarks on result:
other: Redness: Mild at 4 hours. Swelling: None. Discharge: None
Irritation parameter:
cornea opacity score
Basis:
animal #2
Remarks:
Washed Eye
Time point:
other: 1-4 hours
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 24 hours
Remarks on result:
other: Local area of slight clouding at 1-4 hours.
Irritation parameter:
iris score
Basis:
animal #2
Remarks:
Washed eye
Time point:
other: 0
Score:
0
Max. score:
0
Remarks on result:
other: No effects noted
Irritation parameter:
conjunctivae score
Basis:
animal #2
Remarks:
washed eye
Time point:
other: 0
Score:
0
Max. score:
0
Remarks on result:
other: No effects noted
Irritation parameter:
cornea opacity score
Basis:
animal #1
Remarks:
unwashed eye
Time point:
24/48/72 h
Score:
0.3
Irritation parameter:
iris score
Basis:
animal #1
Remarks:
unwashed eye
Time point:
24/48/72 h
Score:
0.3
Irritation parameter:
conjunctivae score
Basis:
animal #1
Remarks:
unwashed eye
Time point:
24/48/72 h
Score:
0.3
Irritation parameter:
cornea opacity score
Basis:
animal #2
Remarks:
washed eye
Time point:
24/48/72 h
Score:
0
Irritation parameter:
iris score
Basis:
animal #2
Remarks:
washed eye
Time point:
24/48/72 h
Score:
0
Irritation parameter:
conjunctivae score
Basis:
animal #2
Remarks:
washed eye
Time point:
24/48/72 h
Score:
0
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Remarks on result:
not measured/tested
Irritant / corrosive response data:
After treating with 4,4'-oxydianiline, washed and unwashed rabbit eyes had slight corneal clouding. The unwashed eye also displayed mild conjunctivitis. Both eyes were normal 1 day after treatment.
Other effects:
None.
Interpretation of results:
GHS criteria not met
Remarks:
Slightly irritating
Conclusions:
This material may cause mild ocular effects, however these are not deemed severe enough to result in classification or labelling.
Executive summary:

A dose of 10 mg of solid test material was placed into the right conjunctival sac of each of 2 male albino rabbits.   After 20 seconds, 1 treated eye was washed with tap water for 1 minute. The treated eye of the other rabbit was not washed.

The unwashed eye also displayed mild conjunctivitis. Both eyes were normal 1 day after treatment.

Effects within the eye are not deemed to warrant classification and labelling. All effects noted were mild and fully reversible in both washed and unwashed eyes within 24 hours.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Additional information

Justification for classification or non-classification

The above studies have all been ranked reliability 1 or 2 according to the Klimish et al system. This ranking was deemed appropriate because the studies were not conducted to GLP (with the exception of the BCOP study) or in compliance with agreed protocols. The reports do not detail a specific method; however it documents dose levels and responses in detail, so is deemed appropriate for use in the support of a formal registration. Sufficient dose ranges and numbers are detailed; hence it is appropriate for use based on reliability and animal welfare grounds.

Justification for classification or non classification

The above results triggered no classification under CLP Regulation (EC No 1272/2008).